rs3851059

Variant names:

• chr10-80270902-G-A
• rs3851059
• ENST00000871619.1:c.*2879C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000871619.1(MAT1A):​c.*2879C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,092 control chromosomes in the GnomAD database, including 6,054 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6054 hom., cov: 32)
• Consequence: MAT1A ENST00000871619.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 9 publications found

Genes affected

MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]

MAT1A Gene-Disease associations (from GenCC):

• methionine adenosyltransferase deficiency

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000871619.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000871619.1		c.*2879C>T		3_prime_UTR	Exon 10 of 10	ENSP00000541678.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42148 AN: 151974 Hom.: 6047 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42174 AN: 152092 Hom.: 6054 Cov.: 32 AF XY: 0.282 AC XY: 20949 AN XY: 74348

African (AFR) AF: 0.205 AC: 8495 AN: 41482

American (AMR) AF: 0.272 AC: 4165 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3472

East Asian (EAS) AF: 0.435 AC: 2253 AN: 5178

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4816

European-Finnish (FIN) AF: 0.312 AC: 3297 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20247 AN: 67972

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.291 Hom.: 21500

Bravo AF: 0.271

Asia WGS AF: 0.384 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.42
PhyloP100		0.036

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3851059; hg19: chr10-82030658;